6-羟基多巴胺和6-氨基多巴胺类似物在生理条件下的分子内环化率。

Intracyclization rates of 6-hydroxydopamine and 6-aminodopamine analogs under physiological conditions.

作者信息

Blank C L, McCreery R L, Wightman R M, Chey W, Adams R N, Reid J R, Smissman E E

出版信息

J Med Chem. 1976 Jan;19(1):178-80. doi: 10.1021/jm00223a035.

Abstract

It is agreed that the neurotoxic action of 6-hydroxydopamine and 6-aminodopamine is related to their ease of oxidation. The initial oxidation products, the p-quinone and p-quinone imine, readily undergo 1,2-intracyclization. These reactions could represent an important loss of active neurotoxic agent available uptake. A variety of substituted 6-aminodopamine analogs was prepared and their formal potentials and cyclization rates were measured accurately. The effect of the balance of ease of oxidation vs. rate of cyclization on their neurotoxicity was examined. The results are in general accord with in vivo lifetimes for 6-hydroxydopamine and 6-aminodopamine in rat caudate nucleus.

摘要

人们一致认为，6-羟基多巴胺和6-氨基多巴胺的神经毒性作用与其易于氧化有关。最初的氧化产物，即对苯醌和对苯醌亚胺，很容易发生1,2-内环化。这些反应可能意味着可用于摄取的活性神经毒性剂的重要损失。制备了多种取代的6-氨基多巴胺类似物，并精确测量了它们的形式电位和环化速率。研究了氧化难易程度与环化速率的平衡对其神经毒性的影响。结果总体上与6-羟基多巴胺和6-氨基多巴胺在大鼠尾状核中的体内寿命一致。